Stanniocalcin 1 (STC-1) is a secreted glycoprotein originally described as a hormone involved in the calcium and phosphate homeostasis in bony fishes. The mammalian homolog of this molecule has been identified as being highly upregulated in an in vitro model of angiogenesis as well as highly expressed at sites of pathological angiogenesis (e.g. tumor vasculature). See, for e.g., Kahn et al., Am. J. Pathol. (2000), 156(6):1887-1900. Its potential role in pathological conditions such as cancer has also been suggested. See, for e.g., Fujiwara et al., Int. J. Oncol. (2000), 16:799-804. Preparation of an antibody for a human STC-1 peptide is reported in Koide et al., Biol. Pharm. Bull. (1998), 21(12):1352-1355. However, the precise role of STC-1 in the angiogenesis process is unclear.
Numerous factors that promote or inhibit angiogenesis have been identified, reflecting the importance of the role of angiogenesis in homeostasis and pathological conditions. See, for e.g., Folkman, Seminars in Oncol. (2002), 29(6) (Suppl. 16):15-18; Ferrara, Seminars in Oncol. (2002), 29(6) (Suppl. 16): 10-14. Well-known angiogenic promoters include vascular endothelial growth factor (VEGF) and hepatocyte growth factor (HGF).
HGF is a mesenchyme-derived pleiotrophic factor with mitogenic, motogenic and morphogenic activities on a number of different cell types. HGF effects are mediated through a specific tyrosine kinase, c-met, and aberrant HGF and c-met expression are frequently observed in a variety of tumors. See, for e.g., Maulik et al., Cytokine & Growth Factor Reviews (2002), 13:41-59. Recent studies have shown HGF to be a potent growth factor implicated in wound healing, tissue regeneration and angiogenesis.
It was also recently reported that HGF, and more potently, HGF in combination with VEGF, synergistically induced vascular morphogenesis in vitro and angiogenesis in vivo (1). The gene expression profile of endothelial cells undergoing HGF and VEGF stimulated morphogenesis using AffmetriX™ oligonucleotide arrays was also analyzed. The homodimeric secreted glycoprotein, Stanniocalcin-1 (STC-1), was shown as one of the most highly upregulated genes in this in vitro model (2). Intense expression of STC-1 was observed in the vasculature of colon carcinomas (2). However, the precise nature of the role(s) of STC-1 in vascularization generally, and angiogenesis specifically, remains heretofore unclear.
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